Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.

Abstract

Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome. Hypo-methylated regions are enriched in areas with heterochromatin binding markers (H3K9me3, H3K27me3), while hyper-methylated regions are enriched in polycomb repressive complex (EZH2/SUZ12) recognizing regions. Altered methylation in promoters, enhancers, and gene bodies, as well as in polycomb repressive complex occupancy and CTCF binding sites are associated with cancer-specific gene dysregulation. Epigenetic-mediated activation of non-canonical WNT/β-catenin/MMP signaling and a YY1/lncRNA ESCCAL-1/ribosomal protein network are uncovered and validated as potential novel ESCC driver alterations. This study advances our understanding of how epigenetic landscapes shape cancer pathogenesis and provides a resource for biomarker and target discovery.

• Authors: Wei Cao, Hayan Lee, Wei Wu, Aubhishek Zaman, Sean McCorkle, Ming Yan, Justin Chen, Qinghe Xing, Nasa Sinnott-Armstrong, Hongen Xu, M Reza Sailani, Wenxue Tang, Yuanbo Cui, Jia Liu, Hongyan Guan, Pengju Lv, Xiaoyan Sun, Lei Sun, Pengli Han, Yanan Lou, Jing Chang, Jinwu Wang, Yuchi Gao, Jiancheng Guo, Gundolf Schenk, Alan Hunter Shain, Fred G Biddle, Eric Collisson, Michael Snyder, Trever G Bivona
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 3675 (07 22 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 32699215 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Heterochromatin
• Histones

Topics

• Aged
• Biomarkers, Tumor (genetics)
• Cell Line, Tumor
• Chromatin Immunoprecipitation Sequencing
• Cohort Studies
• CpG Islands
• DNA Methylation
• Datasets as Topic
• Epigenesis, Genetic
• Esophageal Neoplasms (genetics, pathology, surgery)
• Esophageal Squamous Cell Carcinoma (genetics, pathology, surgery)
• Esophagectomy
• Esophagus (pathology, surgery)
• Female
• Gene Expression Regulation, Neoplastic
• Genomics
• Heterochromatin (metabolism)
• Histones (genetics, metabolism)
• Humans
• Male
• Middle Aged
• Promoter Regions, Genetic (genetics)
• Proteomics
• RNA-Seq
• Whole Genome Sequencing